DESCRIPTION GUKholder, a novel synaptic protein that interacts with the guanylate kinase-like region of DISCS-large, has recently been cloned in a yeast - hybrid screen. In a pattern similar to Discs-large immunoreactivity, GUKholder, immunoreactivity is localized to type I boutons of the Drosophila larval neuromuscular junction. The major goal of this proposal is to characterize one of the components that we believe may be involved in the process of synapse assembly, and to carry out a molecular and functional study using molecular-genetic approaches in the fruitfly Drosophila melanogaster. In this project, GUKholder will be molecularly characterized. The effect of mutations in the GUKholder gene and of targeted over- expression of GUKholder protein on synapse morphology will be determined. The interacting domains of Discs-large and GUKholder will be defined, and a direct interaction between the two proteins will be demonstrated through both molecular and genetic techniques. The unraveling of the role of GUKholder at the Drosophila neuromuscular junction will provide one more piece of the intricate puzzle of how synapses are assembled, how they mature, and how they undergo changes in plasticity in response to the cellular and extracellular environment.